Circulating MicroRNA-155-3p Levels Predicts Response to First Line Immunotherapy in Patients with Metastatic Renal Cell Carcinoma

Overview

Journal Sci Rep

Specialty Science

Date 2024 Apr 13

PMID 38615118

Authors

Maryam Soleimani

Marisa Thi

Sajjad Janfaza

Gizem Ozcan

Sylwia Mazurek

Guliz Ozgun

Corinne Maurice-Dror

Bernhard Eigl

Kim Chi

Christian Kollmannsberger

Lucia Nappi

Affiliations

Soon will be listed here.

Abstract

Predictive biomarkers of response to immune checkpoint-based therapies (ICI) remain a critically unmet need in the management of advanced renal cell carcinoma (RCC). The complex interplay of the tumour microenvironment (TME) and the circulating immune response has proven to be challenging to decipher. MicroRNAs have gained increasing attention for their role in post-transcriptional gene expression regulation, particularly because they can have immunomodulatory properties. We evaluated the presence of immune-specific extracellular vesicle (EV) microRNAs in the plasma of patients with metastatic RCC (mRCC) prior to initiation of ICI. We found significantly lower levels of microRNA155-3p (miR155) in responders to ICI, when compared to non-responders. This microRNA has unique immunomodulatory properties, thus providing potential biological rationale for our findings. Our results support further work in exploring microRNAs as potential biomarkers of response to immunotherapy.

Citing Articles

Blood-based circulating biomarkers for prediction of immune-checkpoint inhibitors efficacy in renal cell carcinoma.

Omri L, Naigeon M, Flippot R, Gavira-Diaz J, Poveda-Ferriols J, Nguyen D Explor Target Antitumor Ther. 2024; 5(6):1199-1222.

PMID: 39465007 PMC: 11502076. DOI: 10.37349/etat.2024.00271.

References

Lucarelli G, Loizzo D, Franzin R, Battaglia S, Ferro M, Cantiello F . Metabolomic insights into pathophysiological mechanisms and biomarker discovery in clear cell renal cell carcinoma. Expert Rev Mol Diagn. 2019; 19(5):397-407. DOI: 10.1080/14737159.2019.1607729. View

Meng L, Xing Z, Guo Z, Qiu Y, Liu Z . Hypoxia-induced microRNA-155 overexpression in extracellular vesicles promotes renal cell carcinoma progression by targeting . Aging (Albany NY). 2021; 13(7):9613-9626. PMC: 8064184. DOI: 10.18632/aging.202706. View

Goc J, Germain C, Vo-Bourgais T, Lupo A, Klein C, Knockaert S . Dendritic cells in tumor-associated tertiary lymphoid structures signal a Th1 cytotoxic immune contexture and license the positive prognostic value of infiltrating CD8+ T cells. Cancer Res. 2013; 74(3):705-15. DOI: 10.1158/0008-5472.CAN-13-1342. View

Bootsma M, McKay R, Emamekhoo H, Bade R, Schehr J, Mannino M . Longitudinal Molecular Profiling of Circulating Tumor Cells in Metastatic Renal Cell Carcinoma. J Clin Oncol. 2022; 40(31):3633-3641. PMC: 9622626. DOI: 10.1200/JCO.22.00219. View

Huber V, Vallacchi V, Fleming V, Hu X, Cova A, Dugo M . Tumor-derived microRNAs induce myeloid suppressor cells and predict immunotherapy resistance in melanoma. J Clin Invest. 2018; 128(12):5505-5516. PMC: 6264733. DOI: 10.1172/JCI98060. View

Raimondi A, Sepe P, Zattarin E, Mennitto A, Stellato M, Claps M . Predictive Biomarkers of Response to Immunotherapy in Metastatic Renal Cell Cancer. Front Oncol. 2020; 10:1644. PMC: 7434861. DOI: 10.3389/fonc.2020.01644. View

Martinez-Usatorre A, Sempere L, Carmona S, Carretero-Iglesia L, Monnot G, Speiser D . MicroRNA-155 Expression Is Enhanced by T-cell Receptor Stimulation Strength and Correlates with Improved Tumor Control in Melanoma. Cancer Immunol Res. 2019; 7(6):1013-1024. DOI: 10.1158/2326-6066.CIR-18-0504. View

Engblom C, Thrane K, Lin Q, Andersson A, Toosi H, Chen X . Spatial transcriptomics of B cell and T cell receptors reveals lymphocyte clonal dynamics. Science. 2023; 382(6675):eadf8486. DOI: 10.1126/science.adf8486. View

Zieren R, Zondervan P, Pienta K, Bex A, de Reijke T, Bins A . Diagnostic liquid biopsy biomarkers in renal cell cancer. Nat Rev Urol. 2023; 21(3):133-157. DOI: 10.1038/s41585-023-00818-y. View

10.

Teng G, Hakimpour P, Landgraf P, Rice A, Tuschl T, Casellas R . MicroRNA-155 is a negative regulator of activation-induced cytidine deaminase. Immunity. 2008; 28(5):621-9. PMC: 2430982. DOI: 10.1016/j.immuni.2008.03.015. View

11.

Mahesh G, Biswas R . MicroRNA-155: A Master Regulator of Inflammation. J Interferon Cytokine Res. 2019; 39(6):321-330. PMC: 6591773. DOI: 10.1089/jir.2018.0155. View

12.

Othman N, Jamal R, Abu N . Cancer-Derived Exosomes as Effectors of Key Inflammation-Related Players. Front Immunol. 2019; 10:2103. PMC: 6737008. DOI: 10.3389/fimmu.2019.02103. View

13.

Ascierto M, McMiller T, Berger A, Danilova L, Anders R, Netto G . The Intratumoral Balance between Metabolic and Immunologic Gene Expression Is Associated with Anti-PD-1 Response in Patients with Renal Cell Carcinoma. Cancer Immunol Res. 2016; 4(9):726-33. PMC: 5584610. DOI: 10.1158/2326-6066.CIR-16-0072. View

14.

Ruggieri F, Jonas K, Ferracin M, Dengler M, Jger V, Pichler M . MicroRNAs as regulators of tumor metabolism. Endocr Relat Cancer. 2023; 30(8). DOI: 10.1530/ERC-22-0267. View

15.

Suganuma N, Segade F, Matsuzu K, Bowden D . Differential expression of facilitative glucose transporters in normal and tumour kidney tissues. BJU Int. 2007; 99(5):1143-9. DOI: 10.1111/j.1464-410X.2007.06765.x. View

16.

Pinthus J, Whelan K, Gallino D, Lu J, Rothschild N . Metabolic features of clear-cell renal cell carcinoma: mechanisms and clinical implications. Can Urol Assoc J. 2011; 5(4):274-82. PMC: 3147044. DOI: 10.5489/cuaj.10196. View

17.

Kozomara A, Birgaoanu M, Griffiths-Jones S . miRBase: from microRNA sequences to function. Nucleic Acids Res. 2018; 47(D1):D155-D162. PMC: 6323917. DOI: 10.1093/nar/gky1141. View

18.

Sharonov G, Serebrovskaya E, Yuzhakova D, Britanova O, Chudakov D . B cells, plasma cells and antibody repertoires in the tumour microenvironment. Nat Rev Immunol. 2020; 20(5):294-307. DOI: 10.1038/s41577-019-0257-x. View

19.

Albiges L, Tannir N, Burotto M, McDermott D, Plimack E, Barthelemy P . Nivolumab plus ipilimumab versus sunitinib for first-line treatment of advanced renal cell carcinoma: extended 4-year follow-up of the phase III CheckMate 214 trial. ESMO Open. 2020; 5(6):e001079. PMC: 7703447. DOI: 10.1136/esmoopen-2020-001079. View

20.

Kim S, Lee E, Jung J, Lee J, Kim H, Kim J . microRNA-155 positively regulates glucose metabolism via PIK3R1-FOXO3a-cMYC axis in breast cancer. Oncogene. 2018; 37(22):2982-2991. PMC: 5978802. DOI: 10.1038/s41388-018-0124-4. View